Monogenic Diabetes Flashcards
Monogenic Diabetes
Diabetes caused by a mutation in a single gene
Mendelian disease
Autosomal dominant or recessive
Types of Monogenic Diabetes
Defects in insulin secretion
- MODY (11 genes identified)
- Neonatal diabetes (~35 genes)
Defects in insulin action
- 9 genes
- Defects in insulin signalling pathway or fat storage
Signs of Monogenic Insulin Resistance
Acanthosis Nigricans
- Hyperinsulinaemic states
- Insulin driven epithelial overgrowth
Defects in fat storage
- Lipodystrophy
MODY
MAturity onset diabetes of the young
Autosomal dominant inheritance
Age of onset usually <25 years
Non-insulin dependent diabetes
MODY aetiology
Glucokinase (~14%)
Transcription Factors (75%)
- HNF1-alpha
- HNF4-alpha
- HNF1- beta
MODYx - undefined (11%)
Glucokinase
Pancreatic glucose sensor within beta cells
Used in first stage. of glycolysis
–> Glucokinase mutation sensing defect
Glucokinase Mutations Presentation
Onset at birth
Stable hyperglycaemia (around 7 mol/L)
Diet treatment
Complications rare
GLucokinase patient
- high fasting glucose
- respond well to glucose challenge
Glucokinase Mutation Treatment
Treatment makes no difference
Is NOT associated with risks- therefore no treatment
Transcription Factor MODY
HNF1-alpha
HNF1-Beta
Adolescence/ young adult onset
Progressive hyperglycaemia
HNF1-alpha mutation treatment
Sulphonylurea (glibenclamide)
Neonatal diabetes Genes (2)
KCNJ11
ABCC8
Neonatal diabetes treatment
Can transition off insulin onto high dose sulphonylurea (glibenclamide)
